The Program Project is focused on the development of integratable microfabricated DNA analysis components. This continuation proposal will develop nanoliter-scale DNA sample handling and analysis technologies for genotyping and for sequencing. The microfluidic, separation, and reaction components of genetic analysis are fabricated on silicon, glass, and/or polymer substrates. To optimize inexpensive design, testing, and production, the devices are made using photolithographic construction techniques. The proposal has three Program Project components, with the following goals: Project 1. Component Development and Refinement. Individual components are identified and are evaluated for suitability in an integrated system. Intensive engineering refinement occurs on a restricted number of component designs. Project 2. Advanced Component and Device Research. The basic engineering information required for advance optical detectors, microfluidic channels, novel fabrication methods, fluid control, surface interactions, and electrophoresis are obtained. Biological sample processing and DNA biochemistry procedures are developed for microscale integrated systems. Core Unit. Fabrication and Instrumentation Support. A central assembly and testing facility is maintained that can rapidly build and test prototypes and components for each of the projects. Experienced research engineers provide fabrication skills, knowledge, and training for the entire Program.